Effects of furocoumarins from Cachrys trifida on some macrophage functions

Phytochemical and biological studies aimed at the discovery and development of novel antiinflammatory agents from natural sources have been conducted in our laboratory for a number of years. In this communication, three natur ally occurring furocoumarins (imperatorin, isoimperatorin and prantschimgin ) were evaluated as potential inhibitors of some macrophage functions invol ved in the inflammatory process. These furocoumarins have been tested in tw o experimental systems: ionophore-stimulated mouse peritoneal macrophages s erve as a source of cyclooxygenase-1 and 5-lipoxygenase, and mouse peritone al macrophages stimulated with E. coli lipopolysaccharide are the means of testing for anti-cyclooxygenase-2 and nitric-oxide-synthase activity. All a bove-mentioned furocoumarins showed significant effect on 5-lipoxygenase (l eukotriene C-4 with IC50 values of < 15 mum. Imperatorin and isoimperatorin exhibited strong-to-medium inhibition on cyclooxygenase-1- and cyclooxygen ase-2-catalysed prostaglandin E-2 release, with inhibition percentages simi lar to those of the reference drugs, indometacin and nimesulide, respective ly. Of the three furocoumarins, only imperatorin caused a significant reduc tion of nitric oxide generation. Imperatorin and isoimperatorin can be clas sified as dual inhibitors, since it was evident that both cyclooxygenase an d lipoxygenase pathways of arachidonate metabolism were inhibited by these compounds. However, selective inhibition of the 5-lipoxygenase pathway is s uggested to be the primary target of action of prantschimgin.